1. Field of Invention
This invention relates to a reagent delivery system for use in the production of radiopharmaceuticals for positron emission tomography (PET). More specifically, it relates to a method of multi-batch production of 18F-labeled glucose, known as fluorodeoxyglucose or “FDG.”
2. Description of the Related Art
Positron Emission Tomography is a powerful tool for diagnosing and treatment planning of many diseases wherein radiopharmaceuticals or radionuclides are injected into a patient to diagnose and assess the disease. For example, the radiopharmaceutical 18F-labeled glucose, known as fluorodeoxyglucose or “FDG”, can be used to determine where normal glucose would be used in the brain. FDG is a labeled compound in which a fluorine-18 ion (18F) is substituted for part of the glucose. FDG labeled in this manner is a desirable radiopharmaceutical because the fluorine-18 is a positron emission nuclide with a half-life period of 109.7 minutes.
The production of PET radiopharmaceuticals requires the use of various reagents and solutions to effect the necessary chemical conversions. The reagents and solutions must be delivered to a reaction vessel, where the conversions take place. The deliveries must be accurate, reproducible and, in addition, there must be minimal cross-contamination between the various reagents. A more detailed discussion of this type of delivery system is disclosed in the above-referenced patent application Ser. No. 09/569,780, filed on May 12, 2000.
Generally, the production of FDG includes the steps of bombarding a target material with a particle beam, mixing the target material with other materials, processing the resulting compound in a reaction vessel, and filtering the product. An accelerator produces radioisotopes by accelerating a particle beam and bombarding a target material, housed in a target system, with the particle beam. To produce FDG, the product of bombardment, fluorine-18 ions, is further processed to produce a substance suitable for injection into the human body. These ions are further processed to produce FDG (2-deoxy-2-fluoro-D-glucose) in a process typically referred to as radiosynthesis.
Well known in the art are various methods for producing FDG. For example, U.S. Pat. No. 4,794,178 issued to Coenen at al. on Dec. 27, 1988 discloses a process for labeling organic compounds with fluorine-18 through a nucleophilic substitution reaction. U.S. Pat. No. 5,169,942 issued to Johnson at al. on Dec. 8, 1992 discloses a method for making FDG that uses a phase-transfer reagent U.S. Pat. No. 5,932,178 issued to Yamazaki at al. on Aug. 3, 1999 discloses an FDG synthesizer that uses a labeling reaction resin column. Although these patents disclose various methods of FDG production, none of these patents teach a method that addresses the specific objects and advantages of the present invention.
Fluorine-18 is a radioactive material to which human exposure should be limited. Also, the particle beam striking the target material is a radioactive process, which should also have limited human exposure. Accordingly, the radiation exposure to persons producing the FDG is an important consideration. Toward this end, efforts have been made to automate the production of radioisotopes, in particular, FDG.
Automation of radionuclide and radiochemical syntheses is discussed in a paper entitled “Introduction: State of the Art in Automated Syntheses of Short-lived Radiopharmaceuticals” by Jeanne M. Link, John C. Clark, and Thomas J. Ruth, Targetry '91, pp 174-185. At page 174, the paper discusses the advantages and disadvantages of the various levels of automation, including manual and remote operation, remote automated operation, and robotic operation. Specifically, the paper identifies the advantages of automation as a reduction of radiation exposure and a reduction of time to perform radiosynthesis. Furthermore, at page 183, the paper describes self-cleaning automated FDG systems.
Many commercially available components can be used to automate the production of FDG. Valves, tubing, and fittings are well known in the art and are well suited to this application. So too are membrane filters. Other components are specially designed for the process. See, for example, the reaction vessel disclosed in the above-referenced patent application Ser. No. 09/569,780, filed on May 12, 2000, and the related patent application Ser. No. 09/795,744 filed on Feb. 28, 2001 by Zigler, et al.
Although the prior art systems have proven successful for the production of FDG, there exists a need for further automation, including the capability of producing multiple batches of FDG with minimum operator intervention. Furthermore, to minimize operator intervention, multi-batch capability requires that the apparatus be self-cleaning and include automated testing of components, such as the membrane filters.
Therefore, it is an object of the present invention to provide an apparatus for performing multiple FDG production runs with a single set up.
It is another object of the present invention is to minimize radiation exposure to the apparatus operators.
It is yet another object of the present invention to provide an apparatus that is easy to handle and economic to use.
Another object of the present invention is to provide an apparatus that is self-cleaning.
Still another object of the present invention is to provide an apparatus which includes means for automating the pressure integrity test of the membrane filtration device used in final product sterilization.